Proteasome-associated autoinflammatory syndrome-5 (PRAAS5) is an autosomal recessive immunologic disorder characterized by the appearance of annular erythematous inflammatory skin lesions on the face and extremities in the first days of life. Additional features include failure to thrive, recurrent fever, microcytic anemia, elevated liver and muscle enzymes, and hypertriglyceridemia. Laboratory studies show leukocytosis with neutrophilia, elevated acute phase reactants, and activation of the type 1 interferon (IFN; see 147660) pathway, consistent with autoinflammation. Treatment with JAK1 (147795) inhibitors results in significant clinical improvement or even clinical remission (summary by Papendorf et al., 2023). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).

Proteasome-associated autoinflammatory syndrome-4 (PRAAS4) is an autosomal recessive immunologic disorder characterized by onset of panniculitis and erythematous skin lesions in early infancy. Additional features include hepatosplenomegaly, lymphadenopathy, fever, generalized lipodystrophy, myositis, and joint contractures, as well as delayed motor and speech development. Autoimmune features, such as hemolytic anemia, may also occur. Laboratory studies show elevation of acute phase reactants and abnormal activation of the type I interferon response. Treatment with the JAK (see 147795) inhibitor ruxolitinib may result in clinical improvement (summary by de Jesus et al., 2019). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).